PLoS ONE (Jan 2015)

The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides.

  • Hussein N Yassine,
  • Olgica Trenchevska,
  • Ambika Ramrakhiani,
  • Aarushi Parekh,
  • Juraj Koska,
  • Ryan W Walker,
  • Dean Billheimer,
  • Peter D Reaven,
  • Frances T Yen,
  • Randall W Nelson,
  • Michael I Goran,
  • Dobrin Nedelkov

DOI
https://doi.org/10.1371/journal.pone.0144138
Journal volume & issue
Vol. 10, no. 12
p. e0144138

Abstract

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Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1 / apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a / apoC-III2 (r = 0.47, p<0.001), apoC-III0b / apoC-III2 (r = 0.41, p<0.001), apoC-III1 / apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms.We conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC- III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.